Images of the interiors of bodies may be acquired using various types of tomographic techniques, which involve recording and measuring radiation from tissues and processing acquired data into images.
One of these tomographic techniques is positron emission tomography (PET), which involves determining spatial distribution of a selected substance throughout the body and facilitates detection of changes in the concentration of that substance over time, thus allowing to determine the metabolic rates in tissue cells.
The selected substance is a radiopharmaceutical administered to the examined object (e.g. a patient) before the PET scan. The radiopharmaceutical, also referred to as an isotopic tracer, is a chemical substance having at least one atom replaced by a radioactive isotope, e.g. 11C, 15O, 13N, 18F, selected so that it undergoes radioactive decay including the emission of a positron (antielectron). The positron is emitted from the atom nucleus and penetrates into the object's tissue, where it is annihilated in reaction with an electron present within the object's body.
The phenomenon of positron and electron annihilation, constituting the principle of PET imaging, consists in converting the masses of both particles into energy emitted as annihilation photons, each having the energy of 511 keV. A single annihilation event usually leads to formation of two photons that diverge in opposite directions at the angle of 180° in accordance with the law of conservation of the momentum within the electron-positron pair's rest frame, with the straight line of photon emission being referred to as the line of response (LOR). The stream of photons generated in the above process is referred to as gamma radiation and each photon is referred to as gamma quantum to highlight the nuclear origin of this radiation. The gamma quanta are capable of penetrating matter, including tissues of living organisms, facilitating their detection at certain distance from object's body. The process of annihilation of the positron-electron pair usually occurs at a distance of several millimeters from the place of the radioactive decay of the isotopic tracer. This distance constitutes a natural limitation of the spatial resolution of PET images to a few millimeters.
In addition to the direct annihilation, also annihilation via electron-positron bound state may exist. Annihilation in the bound state occurs along with creation of the quasi-stable state with the so-called positronium (Ps). Dimensions of positronium are close to the size of the hydrogen atom; however positronium energy structure is significantly different from the energy structure of the hydrogen atom. Positronium, similarly to the hydrogen atom, may be formed in a singlet state of the anti-parallel spins orientation, the so-called para-positronium (p-Ps), with the average lifetime in a vacuum of τp-Ps=0.125 ns, or in a triplet state of parallel spin orientation, the so-called ortho-positronium (o-Ps) with the average lifetime in a vacuum of τo-Ps=142 ns. The lifetime of ortho-positronium τo-Ps decreases to a few nanoseconds in the spaces between cells, while in the case of materials of high electron density, such as metals, o-Ps is not formed at all. Due to the symmetry of charge conjugation, p-Ps undergoes annihilation with emission of an even number of gamma quanta (most often, two quanta), while o-Ps undergoes annihilation with emission of an odd number of gamma quanta (most often, three quanta). The probability of o-Ps creation is three times greater than the probability of p-Ps, creation, whereas the multiple interaction of positronium with environment electrons cause that at the moment of the annihilation, the o-Ps to p-Ps ratio may differ from three. Processes leading to changes in this ratio are called positronium quenching processes. One of the quenching processes is the so-called “pick-off” process, which consists in the fact that the positron bound with electron in positronium annihilates with another electron from the environment. This process involves a quick break of positron-electron “bond” in positronium and immediate annihilation of positron with an electron from the environment. Another example of the process leading to shortening the lifetime of o-Ps is the o-Ps transition into the state of p-Ps. The probability of the positronium quenching processes depends on the size of electron-free volumes, wherein the larger the free volumes in the material, the less the probability of occurrence of the quenching processes and the longer the lifetime of o-Ps.
For free positrons, the direct annihilation with electrons into two gamma quanta is about 370 times more likely than annihilation into 3 gamma quanta, and almost a million times more likely than annihilation into four gamma quanta. Such drastic differences are mainly due to the small value of the electromagnetic coupling constant of 1/137. This means that annihilation usually takes place into two gamma quanta. Annihilations that occurred with creation, in an intermediate state, of ortho-positronium also occur, in the vast majority, into two gamma quanta because they are the result of either conversion of ortho-positronium into para-positronium or interaction of the positron with the electron not bound to it.
Currently, in the PET technique, the phenomenon of producing positronium is neither recorded nor used for imaging. Using conventional PET tomographs gives information on the distribution of a radiopharmaceutical in the body of the object. The detection system of conventional PET tomographs is programmed to record data on annihilation into two gamma quanta of energy of 511 keV.
A PET scanner comprises detection devices used to detect gamma radiation as well as electronic hardware and software allowing to determine the position of the positron-electron pair annihilation on the basis of the position and time of detection of a particular pair of the gamma quanta. The radiation detectors are usually arranged in layers forming a ring around object's body and are mainly made of an inorganic scintillation material. A gamma quantum enters the scintillator, which absorbs its energy to re-emit it in the form of light (a stream of photons). The mechanism of gamma quantum energy absorption within the scintillator may be of dual nature, occurring either by means of the Compton's effect or by means of the photoelectric phenomenon, with only the photoelectric phenomenon being taken into account in calculations carried out by current PET scanners. Thus, it is assumed that the number of photons generated in the scintillator material is proportional to the energy of gamma quanta deposited within the scintillator.
When two annihilation gamma quanta are detected by a pair of detectors at a time interval not larger than several nanoseconds, i.e. in coincidence, the position of annihilation point along the line of response may be determined, i.e. along the line connecting the detector centres or the points within the scintillator strips where the energy of the gamma quanta was deposited. The coordinates of annihilation place are obtained from the difference in times of arrival of two gamma quanta to the detectors located at both ends of the LOR. In the prior art literature, this technique is referred to as the time of flight (TOF) technique, and the PET scanners utilizing time measurements are referred to as TOF-PET scanners. This technique requires that the scintillator has time resolution of a few hundred picoseconds.
Light pulses reaching the scintillator can be converted into electric pulses by means of photomultipliers or photodiodes. Electric signals from the converters carry information on positions and times of the annihilation quanta subjected to detection, as well as on the energy deposited by these quanta.
The standard detection systems of PET tomographs comprises a scintillator layer surrounding the detection chamber, which absorb gamma quanta, being a product of radiopharmaceutical decay, and emits scintillation photons. The most commonly used scintillators are inorganic crystals. In addition, there are known polymer scintillators for use in PET tomographs, as disclosed by patent applications WO2011/008119 and WO2011008118; they enable achieving much better time resolution of the detection system—at the level of 100 ps.
Also hybrid tomographs are known in which the PET technique is combined with other known imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT). Using these devices, hybrid images are obtained, for example, PET/CT or PET/MRI, which provide complementary information: anatomical, functional and morphological. CT tomography provides anatomical image, PET provides metabolic image, while the MR tomography provides morphological image; the PET imaging is particularly advantageous for early detection of metabolic changes—before occurrence of morphological changes detectable via CT or MR imaging. Combination of metabolic (PET) and anatomical (CT) images, or combination of PET image with the morphological (MR) image, is particularly advantageous because it allows precise localization of metabolic changes in individual body parts and determination of degree of these changes.
The parameter determining the degree of metabolic changes recorded by PET is SUV index (Standardised Uptake Value), which expresses the value of the uptake of the radiopharmaceutical in a volume unit (voxel) of the organism in relation to the average value of the uptake of the radiopharmaceutical throughout the body. The higher the SUV the greater the probability of occurrence of cells with disturbed metabolism in a given region of tissue.
The measurement of the lifetime of positrons is used to study the structure of matter at the atomic level. The Positron annihilation lifetime spectroscopy (PALS) allows collect data in the form of positron lifetime spectra, based on which a degree of defect of material of the test sample can be determined. PALS spectroscopes, similarly as PET tomographs, include the scintillators detection system which is connected to the computer. PALS spectrometer measurement consists in introduction of a sample of material with an isotope tracer between detectors and registration of gamma quanta. Positron lifetime information contained in the PALS spectrum is read, for example, by means of a computer program as a result of a numerical analysis consisting in matching the theoretical function to the experimental time spectrum. Such analysis enables determination of the several components of positron lifetime, including ortho-positronium lifetime.
Literature includes numerous publications concerning measurement of lifetime of positrons using the PALS technique.
The article “Badanie zmian wolnych objtości w strukturze polimerowych dwuogniskowych soczewek kontaktowych metod anihilacji pozytonów” [Study of changes in free volume in the polymer structure of bifocal contact lenses using the positron annihilation method” (J. Filipecki et al., Polimery w Medycynie 2010 [Polymers in Medicine 2010], Vol. 40, No. 4, pp. 27-33) published results of research on positron lifetime value in the polymer material used for production of contact lenses. As a source of positrons, the radioactive 22Na isotope was used. Positron lifetime values were calculated using a computer program taking into account the time resolution of the detection system of 270 ps. The best match between the theoretical function and the points constituting the time spectrum was obtained by dividing positron lifetime spectra into three components. The first and the second component were introduced to the program as the following constant values: τp-Ps=0.125 ns and τb=0.36 ns (average lifetime of positrons with free annihilation). For all samples measured using the spectrometer, the third component τo-Ps responsible for the process of annihilation of ortho-positronium related with the process of ortho-positronium “pick-off” by free volume in the polymer matrix was calculated. The study showed that the lifetime of ortho-positronium τo-Ps reflects the average size of free volume present in the polymer matrix.
The article “Influence of neoplastic therapy on the investigated blood using positron annihilation lifetime spectroscopy” (R. Pietrzak et al. NUKLEONIKA 2013, 58 (1): pp. 199-202) describes an experiment in which the PALS spectrometer was used to measure lifetime of positrons in blood samples taken from healthy examined objects and examined objects with cancer. As a source of gamma radiation, 22Na isotope was used. The spectrometer used was characterized by the time resolution of 226 ps. Using a computer program, the average lifetime of ortho-positronium in blood samples of normal and disturbed metabolism was calculated. The results showed that the average radius of the volumes between cells is reduced from about 0.25 nm in blood cells of normal metabolism to about 0.12 nm in blood cells with a disturbed metabolism.
Thus, the larger the ratio of the atom-free volume to the volume of high electron density, the greater the probability that a positron emitted from the radiopharmaceutical creates a bounded state with the electron. The probability of creation and lifetime of positronium depends on the electromagnetic environment (density and momentum distribution of electrons), in which the positron interacts with an electron, which in turn depends on the size of the space between cells; these, in turn, depend on the type of tissue and, in particular, on the stage of development of metabolic disorders (age of ill cells).
It would be desirable to develop a method for measuring the lifetime of positrons in living organisms without the need for invasive sampling, and the development of a tomograph which would enable imaging of positron lifetime distributions as a function of position in the body, providing information about the structure of tissue at the atomic level and allowing for estimating the degree of cell metabolism disorder.